TY - JOUR
T1 - Obesity increases heart failure incidence and mortality
T2 - observational and Mendelian randomization studies totalling over 1 million individuals
AU - Benn, Marianne
AU - Marott, Sarah C W
AU - Tybjærg-Hansen, Anne
AU - Nordestgaard, Børge G
N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions please email: [email protected].
PY - 2022/12/25
Y1 - 2022/12/25
N2 - AIMS: Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice. We tested the hypotheses that high BMI causally influences heart failure incidence and mortality.METHODS AND RESULTS: Using observational and Mendelian randomization causal, genetic analyses, we studied 106 121 individuals from the Copenhagen General Population Study, 18 407 from the Copenhagen City Heart Study, and 977 323 from publicly available databases. In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m2 increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; P < 0.001; n = 124 528; events = 6589) for heart failure incidence, 1.04 (1.03-1.06; P < 0.001; n = 124 528; events = 1237) for heart failure mortality, and 1.01 (1.00-1.01; P < 0.001; n = 124 528; events = 24 144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.19 (1.05-1.36; P = 0.008; n = 118 200; events = 6541) for heart failure incidence, 1.27 (0.82-1.98; P = 0.28; n = 118 200; events = 889) for heart failure mortality, and 1.11 (1.02-1.22; P = 0.022; n = 118 200; events = 16 814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits, the Heart Failure Molecular Epidemiology for Therapeutic Targets, and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.39 (1.27-1.52; P < 0.001; n = 1 095 523; events = 53 850) for heart failure incidence, 1.18 (1.00-1.38; P = 0.05; n = 576 853; events = 2373) for heart failure mortality, and 1.02 (1.00-1.04; P = 0.03; n = 576 853; events = 44 734) for all-cause mortality.CONCLUSION: High BMI causally increases the risk of both heart failure incidence and mortality.
AB - AIMS: Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice. We tested the hypotheses that high BMI causally influences heart failure incidence and mortality.METHODS AND RESULTS: Using observational and Mendelian randomization causal, genetic analyses, we studied 106 121 individuals from the Copenhagen General Population Study, 18 407 from the Copenhagen City Heart Study, and 977 323 from publicly available databases. In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m2 increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; P < 0.001; n = 124 528; events = 6589) for heart failure incidence, 1.04 (1.03-1.06; P < 0.001; n = 124 528; events = 1237) for heart failure mortality, and 1.01 (1.00-1.01; P < 0.001; n = 124 528; events = 24 144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.19 (1.05-1.36; P = 0.008; n = 118 200; events = 6541) for heart failure incidence, 1.27 (0.82-1.98; P = 0.28; n = 118 200; events = 889) for heart failure mortality, and 1.11 (1.02-1.22; P = 0.022; n = 118 200; events = 16 814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits, the Heart Failure Molecular Epidemiology for Therapeutic Targets, and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.39 (1.27-1.52; P < 0.001; n = 1 095 523; events = 53 850) for heart failure incidence, 1.18 (1.00-1.38; P = 0.05; n = 576 853; events = 2373) for heart failure mortality, and 1.02 (1.00-1.04; P = 0.03; n = 576 853; events = 44 734) for all-cause mortality.CONCLUSION: High BMI causally increases the risk of both heart failure incidence and mortality.
KW - Heart failure
KW - Overweight
KW - Obesity
KW - Body mass index
KW - Obesity paradox
KW - Cardiovascular disease
UR - http://www.scopus.com/inward/record.url?scp=85153862632&partnerID=8YFLogxK
U2 - 10.1093/cvr/cvab368
DO - 10.1093/cvr/cvab368
M3 - Journal article
C2 - 34954789
SN - 0008-6363
VL - 118
SP - 3576
EP - 3585
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 18
ER -